PROJECT SUMMARY/ABSTRACT Although the management of ambulatory heart failure (HF) has been revolutionized by evidence-based drug and device therapies, there has been no such parallel progress in the care of patients admitted for worsening HF (WHF). To incentivize health systems to reduce 30-day readmissions, the Affordable Care Act (ACA) launched the Hospital Readmission Reduction Program (HRRP) in 2012, which penalizes hospitals financially if they have higher than expected risk-adjusted 30-day readmission rates for conditions including HF. Although the HRRP has modestly reduced readmissions, this program has had the unintended consequence of shifting a significant fraction of HF-related care to the outpatient setting. Thus, there is a growing interest in the field to disentangle WHF from location of care and move away from using hospitalization as a surrogate for acute decompensated HF. However, little is known about the epidemiology, clinical profile, treatment patterns, and/or outcomes of outpatient WHF. In addition, while the overall survival of ambulatory HF patients has improved dramatically, guideline-directed medical therapy (GDMT) has had minimal impact on impairments in health- related quality of life (HRQOL). Despite this reality, there are few real-world data sources available to describe the trajectory of HRQOL in the ambulatory setting. To address these critical knowledge gaps, we propose (1) to systematically describe the contemporary epidemiology, clinical characteristics, treatment patterns, and outcomes associated with outpatient WHF and (2) to evaluate the impact of an episode of outpatient WHF on generic and disease-specific HRQOL in the context of a fully integrated health care delivery system. The first objective will leverage observational data from a large, state-of-the-art, and validated electronic health record (EHR) system and machine learning algorithms for natural language processing (NLP) to systematically ascertain and comprehensively characterize episodes of outpatient WHF. The second objective will prospectively apply this software-based solution to evaluate generic and disease-specific HRQOL among patients with a recent clinical encounter for outpatient WHF. The overarching goal of this career development award is to provide me with the requisite training in research methodology and project experience to build upon my past successes as a traditional clinical trialist in order to also becoming a leader in health services, implementation science, and pragmatic clinical trials within a learning health system. Strengths of my proposal include my prior relevant training and track record in research, the experience and commitment of my mentors, collaborators, and consultants, and the vast institutional resources and support. In summary, this research proposal will employ innovative analytic approaches to elucidate the epidemiology, clinical features, and outcomes of this previously underappreciated and novel clinical entity. Given the current trend towards managing acute cardiac conditions primarily in the ambulatory setting, these findings have immediate implications for formulating public health policy as well as the design and conduct of future clinical trials.